14‐3‐3ζ binds to and stabilizes phospho‐beclin 1S295 and induces autophagy in hepatocellular carcinoma cells
Identifieur interne : 000B80 ( Main/Exploration ); précédent : 000B79; suivant : 000B8114‐3‐3ζ binds to and stabilizes phospho‐beclin 1S295 and induces autophagy in hepatocellular carcinoma cells
Auteurs : Yufu Tang ; Yibing Zhang ; Shupeng Liu ; Zhongyi Sun ; Chunhui Wang ; Longfei Li ; Wenping Zhou ; Shuqun ChengSource :
- Journal of Cellular and Molecular Medicine [ 1582-1838 ] ; 2019.
Abstract
Data from The Cancer Genome Atlas (TCGA) indicate that the expression levels of 14‐3‐3ζ and beclin 1 (a key molecule involved in cellular autophagy) are up‐regulated and positively correlated with each other (
Url:
DOI: 10.1111/jcmm.14806
PubMed: 31709727
PubMed Central: 6933394
Affiliations:
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Le document en format XML
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<author><name sortKey="Liu, Shupeng" sort="Liu, Shupeng" uniqKey="Liu S" first="Shupeng" last="Liu">Shupeng Liu</name>
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<author><name sortKey="Sun, Zhongyi" sort="Sun, Zhongyi" uniqKey="Sun Z" first="Zhongyi" last="Sun">Zhongyi Sun</name>
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<author><name sortKey="Wang, Chunhui" sort="Wang, Chunhui" uniqKey="Wang C" first="Chunhui" last="Wang">Chunhui Wang</name>
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<series><title level="j">Journal of Cellular and Molecular Medicine</title>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<p>Data from The Cancer Genome Atlas (TCGA) indicate that the expression levels of 14‐3‐3ζ and beclin 1 (a key molecule involved in cellular autophagy) are up‐regulated and positively correlated with each other (<italic>R</italic>
= .5, <italic>P</italic>
< .05) in HCC tissues. Chemoresistance developed in hepatoma cancer cells is associated with autophagy initiation. This study aimed to explore 14‐3‐3ζ’s role in regulating autophagy in HCC cells, with a focus on beclin 1. The co‐localization of 14‐3‐3ζ and beclin 1 was detectable in primary HCC tissues. To simulate in vivo tumour microenvironment (hypoxia), CSQT‐2 and HCC‐LM3 cells were exposed to 2% oxygen for 24 hours. The protein levels of 14‐3‐3ζ and phospho‐beclin 1<sup>S295</sup>
peaked at 12 hours following hypoxia. Meanwhile, the strongest autophagy flux occurred: LC3II was increased, and p62 was decreased significantly. By sequencing the coding area of <italic>BECN 1</italic>
gene of CSQT‐2 and HCC‐LM3 cells, we found that the predicted translational products of <italic>BECN 1</italic>
gene contained RLPS<sup>295</sup>
VP (R, arginine; L, leucine; P, proline; S, serine; V, valine), a classic 14‐3‐3ζ binding motif. CO‐IP results confirmed that 14‐3‐3ζ bound to beclin 1, and this connection was markedly weakened when S<sup>295</sup>
was mutated into A<sup>295</sup>
(alanine). Further, 14‐3‐3ζ overexpression prevented phospho‐beclin 1<sup>S295</sup>
from degradation and enhanced its binding to VPS34, whilst its knockdown accelerated the degradation. Additionally, 14‐3‐3ζ enhanced the chemoresistance of HCC cells to cis‐diammined dichloridoplatium by activating autophagy. Our work reveals that 14‐3‐3ζ binds to and stabilizes phospho‐beclin 1<sup>S295</sup>
and induces autophagy in HCC cells to resist chemotherapy.</p>
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<tree><noCountry><name sortKey="Cheng, Shuqun" sort="Cheng, Shuqun" uniqKey="Cheng S" first="Shuqun" last="Cheng">Shuqun Cheng</name>
<name sortKey="Li, Longfei" sort="Li, Longfei" uniqKey="Li L" first="Longfei" last="Li">Longfei Li</name>
<name sortKey="Liu, Shupeng" sort="Liu, Shupeng" uniqKey="Liu S" first="Shupeng" last="Liu">Shupeng Liu</name>
<name sortKey="Sun, Zhongyi" sort="Sun, Zhongyi" uniqKey="Sun Z" first="Zhongyi" last="Sun">Zhongyi Sun</name>
<name sortKey="Tang, Yufu" sort="Tang, Yufu" uniqKey="Tang Y" first="Yufu" last="Tang">Yufu Tang</name>
<name sortKey="Wang, Chunhui" sort="Wang, Chunhui" uniqKey="Wang C" first="Chunhui" last="Wang">Chunhui Wang</name>
<name sortKey="Zhang, Yibing" sort="Zhang, Yibing" uniqKey="Zhang Y" first="Yibing" last="Zhang">Yibing Zhang</name>
<name sortKey="Zhou, Wenping" sort="Zhou, Wenping" uniqKey="Zhou W" first="Wenping" last="Zhou">Wenping Zhou</name>
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